Thioureidobenzene compounds used as fungicides

ABSTRACT

Thioureidobenzene compounds having the general formula   wherein R and R&#39;&#39; are lower alkyl groups and X is oxygen or sulfur atom have high miticidal and fungicidal activity.

i United States?Patent n 1 Horil et al.

[ 4] THIOUREIDOBENZENE COMPOUNDS USE!) AS FUNGICIDES [75] lnventorszTeisuo Horli; lsao Chiyomaru, both of Shimizu; Selgo Kawada, Fujieda;

Klyoshl Taklta, Shimizu, all of Japan [73] Assignee: Kumlai ChemicalIndustry, Co.,

Ltd., Tokyo, Japan [22] Filed: Apr. 9, 1973 [211 App]. No.: 349,175

[30] Foreign Appllca tion Priority Data 3,714.29) l/l973 Olin 260/926[451 Sept. 2, 1975 Primary Emminer-Albert T. Meyers AssistantExaminer-Leonard Schenkman Attorney, Agent, or Firm-Stevens, Davis,Miller & Mosher [5 7] ABSTRACT Thioureidobenzene compounds having thegeneral formula NH(IINHCOR' wherein R and R are lower alkyl groups and Xis oxygen or sulfur atom have high miticidal and fungicidal activity.

4 Claims, No Drawings rnionneinoaeuzam communes USED AS ruucrcmssnuccrrsm R )2v m-tc nl-lcoa' ll s wherein R and R. shows lower alkylgroups and X shows oxygen or sulfur atom, a method for producing saidcompounds, a method for using said compounds and miticial and fungicidalcompounds containing said compounds as an active ingredient.

The thioureidobenzene series compounds of the presentinvention show ahigh activity for protecting Tetranichiils telz'zrius and alsoprotecting rice plant diseases, such as rice blast (Piriculariaoi'yzae), sheath bright (Pelliculan'a sasaki) and the like; vegetablediseases, such as Selerotinia sclerotiorum, Collelolric/zum lagenarium(cucumber) and the like and fruit diseases, such as Elsinoe fawcetti andDiaporthecitri in oranges, Venturia pirina (pear) and the like. I i

For controlling mites and diseases foragricultural horticultural plants,various pesticides have been developed and used practically butpesticides capable of' being satisfied in view of fungicidal activityand phytotoxicity are few. Furthermore, the use of pesticides has beenrecently very severely regulated in view of the residual toxicity orchronic toxicity as well as the acute toxicity and there have been fewsafely usuable pesticides. Accordingly, the inventors have synthesized alarge number of organic compounds and repeated tests for physiologicalactivity. By such tests it has been found that the compounds of thepresent invention have excellent miticidal and fungicidal activities andare effective for controlling a variety of mites and discases.

As the already known thioureidobenzene series com- I pounds lapanesePatent No. 594,330 has disclosed the compounds having the generalformula I NH CNHCLQR NHC NHC OR wherein X is hydrogen, nitro group,halogen atom or a lower alkyl group and R is a lower alkyl group.

However, the compounds according to the present invention containing aphosphorus atom are novel and have far higher activity than thesealready known compounds and have no phytotoxicity and no toxicityagainst human bodies and domestic animals and can be safely. used.

The compoundsaccording to the present inventioncan be produced by thefollowing reaction formula mncuncok l In the above formulae, R, R -and Xhave the same meanings as described above and Y shows chlorine or:

bromine 'atom and M is ammonium or an alkali metal.

Namely, the above compound (I) and compound (II ethyl ketonej aliphatichydrocaibons, such as p'etro leum ether, ligroin, hexane; aromatichydrocarbons, such as benzene, toluol, Xylol; ethers, such as ethylether, dioxane; esters, such as methyl acetate, ethyl acetate,dirnethylformamide, dimethylacetamide, dimethylsulfoxide and the like.The reaction temperature is 0l00C, preferably 50-80C and the reactiontime is 1-10 hours. From the economic point, the reaction time issufficient after 3-4'hours. It is preferred to add equivalent or aslightly excess amount of the compound (II) based on the compound (1).

The purification may be effected by recrystallizing the synthesizedcompound from an alcohol-water sys tern.

An explanation will be made with respect to the synthesis of thecompounds of the present invention.

EXAMPLE 1 l-diisopropoxyphosphinylthioacetamido-2-( 3- methoxycarbonyl-2-thioureido )benzene ll ll 5 o 30.1 g (0.1 mol) ofl-chloroacetamido-Z-(3- methoxycarbonyl-2-thioureido)benzene and 23.6 g(0.1 mol) of potassium o,o-diisopropylthiophosphate were mixed anddissolved in 250 ml of acetone and the 1 hour and then under a refluxfor 2 hours by heating. After being cooled the reaction solution waspoured 'into ice water to precipitate crystals, which were collected andthen the crystals were dried and recrystalresulting solution was reactedat room temperature for 5 lized from a mixture solvent of benzene andhexane to 1 hour and further under a reflux for 2 hours by heatform 37.1g of white powdery crystals having a melting ing. After cooling, theformed solid was filtered off and point of lO6-l08C. The yield was84.9%. the filtrate was condensed under a reduced pressure. Theprecipitated solid was thoroughly crushed and then EXAMPLE 3 washed withwater and dried. Thereafter, the obtained 101-di-n-propoxyphosphinothioylthioacetamido-2-( 3- product wasrecrystallized from benzene to obtain 36.8methoxycarbonyl-2-thioureido)benzene g of white powdery crystal having amelting point of l22-l24C. The yield was 79.5%. o s

2 NHAcH Su( C; H1 )2 l-dimethoxyphosphinothioylthioacetamido-2-( 3-methoxycarbonyl-2-thioureido)benzene -NHC NH C OC H 3 0 S S 0 it ll NHCH S oCi-I 30.1 g (0.1 mol) of l-chloroacetamido-2-(3- NHC NHC OC H 5methoxycarbonyl-2-thioureido)benzene and 25.3 g H (0. 1 mol) ofpotassium o,o-di-n-propyldithiophosphate 5 o 25 were mixed and dissolvedin 500 ml of acetone and the resulting solution was reacted under refluxby heating for 3 hours while stirring. After being cooled, the 36-0 of1-bf0m0aCetamid0-2-(3- formed solid was filtered off and the filtratewas conethoxycarbonyl-2-thioureido )benzene was dissolved in densedunder a reduced pressure. The resulting precip- 3 ml Qfacetonitrile andto thefesultmg Solution was itates were recrystallized from a solutionof methyl aladded dropwise a solution of 18.0 g (0.1 mol) of socohol andwater in a mixture ratio of 3:1 to obtain 42.7dium.o,0-dimethyldithiophosphate in 100 ml of acetO- g of white powderycrystal having a melting point of nitrile while being cooled with waterand stirred. The 98-100C. The yield was 89%. temperature did notsubstantially rise. After the addi- In the same manner, the followingcompounds are tion, the reaction was effected at room temperature forproduced.

Com- Chemical MP pound No. Structure name (BP) C Appearance 0 Hl-dimethoxyphosphinyl- NHCCHZSHOCHH)2 thioacetamido-Z-(B- light brown Imethoxycarbonyl-Z- l06l l0 powdery crystal Q: NHC N coc H3thioureido)benzene II II S O H ldimethoxyphosphino- NHCCH,SP(OCH;|)2thioylthioacetamidoal 15-] 19 light brown 2 (3-methoxycarbonyl-2-powdery crystal NHC N Hc 0c H 3 thi0ureido)benzene Ii S Ol-diisopropoxyphosphinyl- 3 NHCCH SWOC;,H iso) fl1i0acemmido-2-( 3-l22-l24 White powdery methoxycarhonyl-Z- crystal Q NHC N c 0c H 3thioureido)bcnzene II II S O o (U: l-di-n-propoxyphosphino- 4 NHCH-,SP(OC;,H;-n). thioylthioacetamido2- 98-]00 white powderyB-methoxycarbonybl crystal Q N N Hc 0c H 3 thioureido)benzenc II IIContinued Com- Chemical MP pound No. Structure name (BP) "C Appearancel-dusopropoxyphosphmo- 5 NHCCH,SP(OC;,H;-iso) thioyIthioacetamido-Z- 889l light brown i 1 (3 methoxycarbonyl-2- powdery crystal NHC NHCOC H3thioureido)benzene II n S O H l-di-n-propoxyphosphinyl- NHCCHSP(OC;,H,n). thioacetamidoQ-(B- more than brown 6 methoxycarbonyl2140/0. l glutin-like NHC NHCOC H thioureido)benzene rnmHg substance l IIS O l o o l-din-butoxyphosphinyll NHCCH SP(OC,H n thioacetamido-2-( 3-more than brown 7 methoxycurbonyl-Z- l 50/().4 glutin-like C NHCOC Hthioureido)benzenc mmHg substance II II 3 S O H I l-di-n-hutoxyphosphino8 NHCCH SP(OC H,.n) thioylthioacetamido-Z- 85 87 light brown(3-methoxycarbonyl-2- powdery crystal NHC NHCOC H3 thiourcidojbenzene vII II S O H l-di-sec-butoxyphosphino- J NHC C H-;SP( OC H,,sec)thioylthioacctumidoQ- 79 82 light brown (3-methoxycarb0nyl-2- powderycrystal NHC NHcoc H3 thioureido)benzene II II S O l-dimethoxyphosphinmH] NHCCH- SHOCHM thioylthioacetamidoilob-J08 white powdery(3-ethoxycarhonyl-2- crystal NHC NHCOC thioureido henzene II II S O Hl-diethoxyphosphinyllight brown I l NHCCH- -SP(OC H thioacetamido2-( 3-98-10] prism-like ethoxycarbonyl-Z- crystal NHCNHCOC 2 5thioureido)benzene i ll u O O l H l-diisopropoxyphosphinyl- 12 NHCCHSP(OC -,H,-iso) thioacetamid0-2-( 3- 107.5-l H White powderycthoxycarhonyl-Z- crystal N H c N CDC 2 H 5 thiuurcido)benzene II ll S 0When thecompounds according to the present invention are used asarhiticide or a fungicide, the compounds are mixed with ajsuitablccarrier and formulated into wettable powder; dust, granule andemulsifiable concentrate. These compositions may be used directly orafter being diluted with a diluent or mixed with other materials.Further, the compounds of the present invention can be used more widelyby using them together with other fungicides and insecticides.

The carrier may be solid or liquid. When the carrier is used togetherwith surfactants or dispersants, pesticidal compositions having moreimproved property can be obtained. As the solid carrier, use may be madeof talc, diatomaceous earth, silica gel and other various materials. Asthe liquid solvent, use may be made of solvents ordinarily used for thepreparation of pesticidal compositions, such as methyl ethyl ketone andother aliphatic compounds, and xylene and other aromatic compounds.

As the surfactants, use may be made of emulsifiers, such aspolyoxyethylenealkylaryl ether, polyoxyethylenealkyl ether,polyoxyethylene aliphatic acid ester, alkylarylsulfonate,polyoxyethylenepolyalkyldiphenyl ether, etc. alone or in admixture;wetting agents, such as alkylarylsulfonate, polyoxyethylenealkylarylether, lauryl sulfate, polyoxyethylenealkylarylsulfonate, etc.;dispersants, such as ligninsulfonate, PVA, CMC, a condensate ofalkylarylsulfonate with formaldehyde, etc.

The compound of the present invention is mixed with a solid carrier toprepare a dust. Further, the compound is mixed with a solid carrier and13% of a surfactant as a wetting agent to prepare a wettable powder,which is diluted with water and used. The compound is added with asolvent and -15% of a surfactant as an emulsifier to prepare anemulsifiable concentrate, which is diluted with water to a suitableconcen- "tration and used. Furthermore, the compound can be mixed with asolid carrier, a surfactant and other adjuvants, and can be used in theform of a granule.

The invention will be further explained in detail with reference to thefollowing examples for formulating various compositions. The additivesand active ingredients can be varied within a wide range.

EXAMPLE 4 Wettable powder Fifty parts (hereinafter, parts means byweight) of the above compound No. 2, parts of diatomaceous earth, partsof talc and 5 parts of a wetting agent, Sorpol (trademark, of a mixtureof sodium dinaphthylmethanedisulfonate and sodium ligninsulfonate, madeby Toho Kagaku Co.) were homogeneously mixed and milled to prepare awettable powder.

EXAMPLE 5 Dust Three parts of the above compound No. 1, 47 parts oftalc, 47 parts of clay and 3 parts of white carbon were mixed and milledto prepare a dust.

EXAMPLE 6 Granule Twenty parts of the above compound No. 4, 2 parts ofsodium dodecylbenzenesulfonate and 78 parts of diatomaceous earth werehomogeneously mixed and milled, and then kneaded together with 25 partsof water. The kneaded mixture was extruded through an extrusion typegranule forming machine to obtain granules, which were dried and sievedto prepare a granule composition.

The excellent miticidal and fungicidal activities of the compounds ofthe present invention will be explained with respect to the followingtests.

Test 1 Experiment of activity for preventing rice blast An unglazed pothaving a diameter of 2 cm planted with 20 plants of 4-5 leaf stage ofyoung rice plants (species: AlCHl ASAHl) was mounted on a turntable andon the rice plants was sprayed a dispersion obtained by diluting thewettable powder according to the present invention prepared in the aboveExample 4 with water under a spraying pressure of 0.5 Kg/cm by means ofa spray gun in an amount of 30 ml per pot.

3 days after the spraying, a suspension of Piricularia oryzae spores inwater formed by successively inoculating rice blast on rice plant in agreenhouse and adjusting the concentration of spores so as to contain 20spores in a visual field (l5 10 times) of a microscope, was sprayed onthe rice plants in an amount of 5 ml per pot.

After the inoculation,-the pot was placed in a wet room (saturatedhumidity, 24C) made of vinyl sheet for 24 hours and then transferredinto a greenhouse which was kept at a high temperature to propagate thediseased spots. Seven days after the inoculation, the number of thediseased spots was counted with respect to 10 leaves per pot tocalculate the protective value. The obtained results are shown in thefollowing Table Number of Number of diseased spots diseased spotsProtective in untreated pot in treated pot value (70) [Number ofdiseased spots in] x loo untreated pot Table 1 Protective Com-Concentration value Phytotoxicity pound No. (ppm) 1 250 96.8 No 2 250100 No 3 250 94.7 No 4 250 100 No 5 250 100 No 6 250 98 No 7 250 99.2 No8 250 I00 No 9 250 I00 No 10 250 I00 No l l 250 95.1 No l2 250 99.2 NoBlastin* 250 95.2 No

*Pentachlorobenzylalcohol Test 2 rice plant A pot having a diameter of 9cm planted with three groups of 5-6 leaf stage rice plants (species:KIN- MAZE), one group of which has 3 plants was mounted on a turntableand on the rice plants was sprayed a dispersion obtained by diluting thewettable powder prepared in Example 4 with water under a sprayingpressure of 1.0 Kg/cm by means of a spray gun in an amount of 30 ml perpot. Next day the spraying, Pellicularia sasaki was inoculated on thethus treated rice plants. The inoculation of Pellicularia sasaki was conducted in the following manner. Pellicularia sasaki was cultured in aPetri dish containing potato agar medium for 3 days and then the mediumwas punched out into disks having a diameter of 10 mm. Then, the diskwas inserted between the base portions of the rice plants to morbidity.

9 10 efiect the inoculation. After the inoculation, the pot Table 3 wasmaintained at a high temperature in a greenhouse. for 10 days. Then thenumberofJthe diseased spots was Protective counted with respect to 9stems per pot to calculate the mff 2??? a? Phymwxmy protective valueaccording to the following formula. 5

"1 250 91 No 2 250 93 No LL 3 250 84 No Number of diseased spots in V 4'250 82 No Protective treated pot i 5 9 i 250 68' No value (3) Number ofdiseased spots in x 1O :8 untreated pot 8 250 9 No A Y Y 9 250 93 No Theobtained results are shown in the following Table l i 3? 2, L 12 250 90No l Compound (A)* 250 2| No Table 2 i w r (A'): l.2-bis(" L 5. J inJapanese Patent No. 594.330. Protective v 'v Com- Concentration .yvaluev Phytotoxicity pound Test 4 No. (ppm) ('7 Experiment of activityfor preventing cucumber 1 125 100 t No Colletotrichum lagenarium 2 12598.2 No i i 3 12s 99.1 No when l5 seeds of cucumber (species: SAGAMI i 1HANPAKU )'.were sown in an unglazed pot having a di- 5 125 I00 .No' 6 i'25 @100. 25 axneter of 4 cm a nd cotyledon appeared, a dispersion 7 125No obtained by diluting the wettable powder prepared in 8 I25 100 N0 theabove Example 4 with water was sprayed on the eu- '8; cumber, seedlingsunder a spraying pressure of 1.0 H 25 r :3 No Kg/cm by means of a spraygun in an amount of 20 ml 12 I25 100 No per pot while the pot beingmounted on a turntable. i 5 2 After 24 hours, cucumber Colletorrichumlagenarium asozme :32'- 98.8 i No quid i was sprayed and inoculated onthe cucumber plants. com Collelatrichum Iagenarium had been cultured oncorn "9" agar medium for 10 days to obtain spores. Then, the T i I H an,mm Omaha eumnic acid 35 spore concentration had been adjusted so as tocontain muny 0 me n '200 spores in a visual field (l5 l0 times) of amicroi .Test3 1 r scope. The thus formed spore suspension was sprayedExperiment of activity for preventing Selerotinia on' the cucumberplants in an amount of 4 ml per pot. scleroriorum of haricot bean Afterthe inoculation, the pot was placed in a wet room 4 D t 0 Q on 2 1e shafico plamgd u -Un 40 isaturatttzln gumldlty, i4 C21 made ofvinylhsheet ford4 pot having a diameter of 15"e'rn was sprayed adisperours transfne a green ouse, an sion obtained by diluting thewettable powder prepared days the f of the dfseased in the above Example4 with water in an amount of 15 5pm? r F The number of the dlseased mlAft one y said bean praht'was inoculated with spots was counted withrespect to cotyledons of 10 cudisk (diameter, 6 mm) of pqtato extractagar medium 45. cumber seedlings and the protective value was calcuinwhich Selerorinia sclerotrorum had been cultured. 4 lated-The Qbtamedresults are Show" the fOnowmg days after the inoculation, the morbiditywas deter-' Table rnined according to th elfollowing standard. Theresult Number of diseased 5pm IS shown in the following Table 3.Protective in treated pot I X 100 Estimating standard of morbidity.value Number of diseased spots 0: Not diseased. v pm 1: Diseased justunder the inoculated portion or around said portion. Table 4 2: Diseasedto about one-fifth of the inoculated leaves. Protective 3: Diseased toabout two-fifths Of the inoculated Compound Concentration valuePhytotoxicity leaves. No. (ppm) (9H 4: Diseased to about three-fifths ofthe inoculated 1 100 No leaves. 2 250 mo No 5: Diseased to aboutfour-fifths of the inoculated 6o 2 33' leaves. 5 250 100 No i a 250 100No i 7 250 100 No u N Protective ()Xu,+l u 5X, x ,0 g :8 value ('26)SXEu, l() 250 No ll 250 98.6 No l2 250 100 No u Number of leaves of theestimating standard of compuund (A) 250 903 No "concentration' and theimin'ers e'd' leaf was under Test Experiment of activity against adultsor ova of Tetrdhichus t elar ius Tw fo m at ng a a. a .v a 1 The firstleaf of haricot bean grown in a pot having a diameter of cm was cut offin circular forms by a 3 cm leaf punch and 5 Tetranichus telarius adultswere infested on each the cut circular leaf and allowed to be blown Theadults were removed 24 hours after the infesting in order to make theova age to be uniform. The ova deposited leaf .was immersed for 10seconds in an aqueous dispersionobtained by diluting the wettable powderprepared in Example 4 with water in t oa given concentration.The-percentage of combating ovawas determined as follows. The number ofovawas previously counted prior to the blowing and when all the ova inthe untreated leaf were blown, the number of the blown ova was counted:"7 2. Test for combating adults:

Haricot bean leaf in stage was punched by a leaf punch and the punchedleaf was immersed for 10 secpiids in a dispersion olbtaihed by dilutingthe wafbge prepared 1e with 'water into a g' "en air and infested ivyith thfe ad ults After' days, the 'num'- 5a of thelivin g'adults wasldetermiri edlj, g Qln boththe'" tests for ovaand adult, they werei'riad e in; replications in which one zone was 50 adults; v Theobtained result is shown in the following Table 5.

Percentage of I combating ova Percentage of Compound Concentrationcombating adults Y -"NHccH 's| oR i;

-NHCNHCOR l II wherein R' and arelower alk yl and X isoxygen orsulfuryas the ative ingredient,;and

a carrier therefore. 7 2. The composition of claim 1 wherein saidthioureidobenzene-compound-is: n a

' NHccH,sP oR -NHC NHCOR .r. v, a, n "I wherein Rand R are lower alkyl.

3. The composition 'of claim .wherein said thioureidobenzene compound iswherein R and R are lower alkyl.

4.' A method for controlling:fungi-- on "plants which No. (pp (7 v H 1.I V, 1- .rv: compnses n. V

r 40 applying a .fungiqi dally effective amount pf a thil v 2oureidobenzene compound having the formula; i

H00! v r s v 500a. v I00 6 500 100 7 -500 not)" 8 50o too r 9 I 500 100lO--'- -500 99,2 11 500 100' 12 500 100 Untreated 0 What is claimed is:l. A fungical composition comprising a fungicidally effective amount ofa thioureidobenzene compound having the formula wherein-R and R areloweralkyl and X is 'oxygen 'or sulfur g t6 s'aid'plants.

1. A FUNGICAL COMPOSITION COMPRISING A FIGICIDALLY EFFECTIVE AMOUNT OF ATHIOUREIDOBENZENE COMPOUND HAVING THE FORMULA
 2. The composition ofclaim 1 wherein said thioureidobenzene compound is
 3. The composition ofclaim 1 wherein said thioureidobenzene compound is
 4. A method forcontrolling fungi on plants which comprises applying a fungicidallyeffective amount of a thioureidobenzene compound having the formula